Parasites and microbial organisms that gain entry into human and animal hosts by (a) penetrating through the skin or (b) being xe2x80x9cdeliveredxe2x80x9d via other vectors (e.g., mosquitoes, ticks, flies, etc.) through the skin, are responsible for a very large proportion of disease. An example of an organism penetrating the skin is schistosomiasis, which is a life threatening infection of humans and animals in many tropical and subtropical parts of the world. According to the World Health Organization (WHO) estimate there are currently over 200 million people infected with this parasite and another 600 million at risk. [WHO Expert Committee on the Control of Schistosomiasis: Public Health Impact of Schistosomiasis Disease and Mortality Bulletin of the World Health Organization, 71:657-662, 1993]. Travelers visiting such endemic areas are at greater risk of acquiring the disease and disseminating it further. Skin is the only known route of entry for this parasite into humans and animals with the infective stage (cercariae) of the parasite having the ability to penetrate intact skin within a matter of minutes after water contact. Therefore, any agent that will interfere with entry of cercaria into the skin will essentially prevent schistosomiasis. Another disease condition called xe2x80x9cswimmers itchxe2x80x9d or xe2x80x9ccercarial dermatitisxe2x80x9d is caused by inadvertent entry of the cercariae of animal schistosomes (i.e. Trichobilharzia ocellata) into human skin resulting in severe dermatitis. This condition is widely prevalent in the many fresh water lakes of the United States, Asia, and New Zealand as well as the rice paddies of Asia. Similarly, hookworm parasites, particularly Necator americanus, directly infect man and animals by penetrating intact skin. The mature worm lives in the stomach, daily consuming a blood meal and contributing to the malnourishment of the host. Further, infection with this parasite is often attended with other disease states. It is conservatively estimated that approximately one billion people may be infected with hookworm.
Arthropods and related species xe2x80x9cdeliverxe2x80x9d parasites and other microbial disease-producing organisms through the skin after biting the host. Best known and most problematic is malaria, which effects millions of people in tropical and subtropical regions of the world. According to WHO estimates, malaria ranks among the top five leading causes of death worldwide. Over the past 20 years the malaria problem has been exacerbated by the appearance of drug resistant strains. Mosquitoes are also known to be carriers of non-parasitic diseases such as Dengue, Yellow Fever, and other conditions. Various species of ticks are responsible for Lyme Disease, Rocky Mountain Spotted Fever, Ehrlichiosis, Colorado Tick Fever, Tularemia, Relapsing Fever, Powassan Encephalitis and tick paralysis.
According to the Centers for Disease Control and Prevention (CDC) more cases of tick borne disease were reported during the 1994-1997 period than the combined total of cases reported for measles, mumps, whooping cough, rubella, diphtheria, cholera, leptospirosis, leprosy, plague, tetanus, trichinosis, typhoid fever, giardiasis, and Legionnaire""s disease in the U.S. Ticks infect humans and animals by taking a blood meal thereby introducing their own infected saliva into the host.
Sand flies will also bite human hosts thereby introducing the organism responsible for human Leishmaniasis. There are many additional examples of arthropods (black flies, gnats, chiggers, deer flies, fleas, tsetse flies, reduviid bugs, etc.) that can cause disease through skin bites.
Independent of disease caused by these arthropods and related species their bites are the cause of significant annoyance and discomfort both in tropical climates and more temperate summer climates. The economic impact of all these diseases and discomfort is significant.
The invention is directed to materials and methods for preventing parasitic diseases. In particular the invention is directed to preventing parasitic diseases which are caused by skin penetrating parasites or by parasites that are introduced into a host animal via an arthropod vector. The invention is also directed to material and methods for repelling insects.
Exemplary parasitic disease include Schistosomiasis swimmers itch and diseases caused by Ancylostoma species, Necator species, Strongyloides species and others. Exemplary biting insects include ticks, sand flies, black flies, triatomid bugs, reduviid bugs, fleas, mosquitoes, and other species of arthropod vectors that transmit infectious diseases in humans and animals.
Materials useful in the practice of the present invention include N,N-diethyl-m-toluamide (DEET) and formulations of DEET which prolong the effectiveness of DEET and which require lower concentration doses than those commonly used. Such formulation include DEET enveloped in liposomes or in combination with polymers and polyolprepolymers. Liposomes/DEET formulations according to the present invention do not require the presence of an xe2x80x9cenvironment enhancingxe2x80x9d chemical like pyridinethione (ZPT) as a skin anchoring chemical moiety for increasing their effectiveness. The formulations described above are also useful for repelling biting insects.
Liposomes may be anionic, cationic or neutral. Preferred liposomes are cationic liposomes comprising L-xcex1-phosphatidylcholine, stearylamine and cholesterol. Preferred concentrations of DEET include from about 1% to about 50% w/v. More preferred are concentrations from about 7% to about 10%. Most preferred is a concentration of about 7.5% DEET. Preferred polyolprepolymers of the invention include polyolprepolymer 2 and polyolprepolymer 15.
The present invention also embodies Liposome/DEET formulations with other insect repellants and ant-parasitic drugs.